Antibiotics Therapy for Musculoskeletal Infections

Mechanism

Antibiotics are categorized according to their mechanism of action, namely:

  1. cell wall active
  2. ribosomal active
  3. RNA active
  4. DNA active
  5. antimetabolites
  6. reducing compounds

Cell Wall Active Antibiotics

Penicillins

  • Active against
    • S. pyogenes, S. agalactiae
    • Good anaerobic spectrum = Clostridia except Bacteroides
    • Increasing resistance from S. pneumoniae
  • Side effects
    • Hypersensitivity reactions namely anaphylaxis, bronchospasm, hives
    • Potential interstitial nephritis, Coombs positive haemolytic anaemia
  • Parenteral penicillinase resistant penicillins
    • methicillin, nafcillin, isoxazolyl penicillins (flucloxacillin, dicloxacillin, cloxacillin) are resistant to Staph beta lactamase
  • Aminopenicillins = ampicillin, amoxycillin
    • Active against Entercocci & highly susceptible E. coli + Proteus
    • Not stable to beta lactamase
  • Ticarcillin
    • Active against Pseudomonas, Enterobacter, Serratia but not Klebsiella
    • Side effect of platelet dysfunction
  • Extended spectrum penicillins = piperacillin + mezlocillin
    • Act in synergy with aminoglycosides against Pseudomonas

Beta lactamase inhibitors

  • Clavulanic acid, sulbactam, tazobactam inhibit beta lactamase produced by
  • gram positives notably S. aureus + S. epi
  • gram negatives namely E. coli, most Klebsiella + Bacteroides
  • Beta lactamase is situated in periplasmic space & is chromosome + plasmid induced
  • Clavulanic acid + amoxycillin = Augmentin
  • Clavulanic acid + Ticarcillin = Timentin
  • Tazobactam + piperacillin = Zosyn

Cephalosporins

Divided into generations

  • 1st
  • Cephalothin, cephazolin, cephapirin

Active against S. aureus, S. epi, Streptococci but limited activity against gram negatives

Generally safe but occasional eruptions, phlebitis, diarrhea

Cephazolin has longest half life of 1st generation cephalosporins

  • 2nd
  • Cefoxitin, cefotetan, cefuroxime

Active against anaerobes & to lesser extent gram negatives

  • 3rd
  • Ceftriaxone, cefoxitime, ceftazidime are beta lactamase resistant

Active against gram positives (except Enterococci) + Enterobacter

  • 4th
  • Cefepime is active against gram positives + Pseudomonas
  • Low prevalence of adverse reactions
    • 3-7% cross reactivity in penicillin allergic patients
    • Type 1 immediate hypersensitivity = bronchospasm, hives, rashes within 3-5 days
    • 3% patients with Coombs positive anaemia
    • 1-7% patients with abnormal LFTS
    • antibiotic associated colitis

Other beta lactam antibiotics

  • Aztreonam iv use only, active against Enterobacter + Pseudomonas
  • Imipenem active against S. aureus, S. epi, Strep

Vancomycin

  • Antibiotic of choice in penicillin + cephalosporin allergy
  • Active against S. aureus, MRSA, S. epi, Enterococci
  • Vancomycin resistant Enterococci (VRE) reported
  • Adverse effects
  • Red man syndrome = head + neck + trunk flushing & hypotension when infusion given over <1 hour
  • Nephrotoxicity, ototoxicity, neutropaenia, thrombocytopaenia

Ribosomal Active Antibiotics

Clindamycin

  • Active against
    • Bacteroides but not Clostridia (except C. perfringens)
    • S. aureus, coagulase negative Staph, Strep
  • Good bone + abscess penetration
  • Adverse effects = diarrhea + pseudomembranous colitis in 8% (C. difficile)

Macrolides

  • Erythromycin, clarithromycin, roxythromycin work at ribosomal level & are bacteriostatic
  • Active against Strep, Mycoplasma, Listeria, Legionella, Chlamydia
  • Adverse effects = generally safe but GIT upset
  • Induces hepatic cytochrome P450 complexes = ↑drug metabolism

Tetracyclines

  • 3 groups
  • short acting = tetracycline
  • intermediate acting = demeclocycline
  • long acting = doxycycline, minocycline (minocycline + rifampicin for MRSA)
  • Active against uncommon diseases mycoplasma, rickettsia, Lyme disease
  • Adverse effects = GIT upset, hepatotoxicity, teeth discolouration, photosensitivity

Aminoglycosides

  • Gentamicin, tobramycin, amikacin, netilmicin
  • Active against aerobic gram negatives
  • Adverse effects = nephrotoxicity, ototoxicity (hearing loss, tinnitus, vestibular problems, gait disturbance)

RNA Active Antibiotics (Rifampicin)

  • Most active antistaphylococcal agent known
  • Rifampicin alone rapidly produces rifampicin resistant subpopulation
  • Fusidic acid or cotrimoxazole or minocycline + rifampicin for MRSA
  • Adverse effects = orange body fluids, GIT upset, hepatitis
  • Must be taken on empty stomach
  • Induces hepatic microsomal enzymes

DNA Active Antibiotics (Fluoroquinolones)

  • 2nd generation quinolones = ciprofloxacin active against gram negatives. No activity against Strep + anaerobes
  • Oral ciprofloxacin provides excellent serum concentrations
  • Adverse effects = tendonitis with Achilles tendon rupture, photosensitivity but overall toxicity is low

Antimetabolites

  • Cotrimoxazole is active against gram negatives
  • Adverse effects = GIT upset, acute haemolytic anaemia, aplastic anaemia, thrombocytopaenia, hypersensitivity (erythema multiforme + nodosum, urticaria)

Reducing Compounds (metronidazole)

  • Lead to toxic free radical formation
  • Active against all anaerobes (anaerobes lack protective superoxide dismutase + catalase)
  • Good absorption + tissue penetration
  • Adverse effects = metallic taste, pseudomembranous colitis, disulfiram reaction with alcohol